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Bitter taste receptors (TAS2R) and EP4 prostaglandin receptors are emerging targets for new bronchodilators.Heat shock protein HSP20 is a cAMP-dependent inhibitor of bronchoconstriction.Rho kinase signaling is also a promising target for novel bronchodilator therapy.Statins may inhibit small G-protein signaling to promote bronchodilation.New epigenetic targets include histone modifying enzymes and microRNAs.Significant advances in understanding the cell and molecular biology of inflammation and airway smooth muscle (ASM) contractility have identified several potential novel targets for therapies of asthma. New agents targeting G-protein coupled receptors (GPCRs) including bitter taste receptors (TAS2R) agonists and prostaglandin EP4 receptor agonists elicit ASM relaxation. The cAMP/PKA pathway continues to be a promising drug target with the emergence of new PDE inhibitors and a novel PKA target protein, HSP20, which mediates smooth muscle relaxation via actin depolymerization. Smooth muscle relaxation can also be elicited by inhibitors of the RhoA/Rho kinase pathway via inhibition of myosin light chain phosphorylation and actin depolymerization. Targeting epigenetic processes that control chromatin remodeling and RNA-induced gene silencing in airway cells also holds great potential for novel asthma therapy. Further investigation may identify agents that inhibit smooth muscle contraction and/or restrain or reverse obstructive remodeling of the airways.